Irreversible Cell Injury and Cell Death

Question 1

The cellular response to injury depends on?

Answer 1

1. The type of cell
2. The severity
3. The duration

Question 2

Susceptibility of cells to Hypoxia

Answer 2

‣ High
• Neurons: (3-5 min)
‣ Intermediate
• Myocardium, hepatocytes, renal epithelium (30 min - 2 hr)
‣ Low
• Fibroblasts, epidermis, skeletal muscle (many hrs)

Question 3

What happens in the case of severe and persistent injury?

Answer 3

Severe and persistent injury —> point of no return.

1. Inability to reverse mitochondrial dysfunction
2. Severe dysfunction of cell membranes (Lysosomal membranes → Lysosomal enzymes)
3. Increased intracellular calcium levels

Question 4

What can necrosis lead to?

Answer 4

• Necrosis —> Pathological (point of no return) —> Oncotic necrosis (oncosis [derived from onkos, meaning swelling).

Question 5

What does apoptosis lead to?

Answer 5

Physiologic cell death/Programmed cell death.

Question 6

Name and explain three situations in which the body has reached the point of no return?

Answer 6

◦ Ultrastructural
‣ Swelling
‣ Rupture of plasma membrane and organelles (leakage of contents)
‣ Rupture of nucleus
‣ Mitochondria are swollen and develop amorphous densities
◦ Microscopic
‣ Hypereosinophilic cytoplasm (due to denatured proteins and loss of ribosomes)
‣ Nuclear changes:
‣ Pyknosis (nuclear condensation with shrinkage and intense basophilia)
‣ Karyorrhexis (nuclear fragmentation)
‣ Karyolysis (nuclear dissolution or loss)
◦ Gross (macroscopic)
‣ In general:
• Swelling and pallor (soon after cell death)
• Loss of structural detail and demarcation from adjacent viable tissue
• Discolored (usually white)
• Soft
‣ It varies a lot; it depends of: tissue involved, the nature of the injurious agent, and the time elapsed after cell death.
‣ Necrosis has been classified as coagulative, caseous, liquefactive or lytic, and gangrenous

Question 7

Microscopic images here

Question 8

What are the types of oncotic necrosis?

Answer 8

1. Coagulative necrosis
2. Caseous necrosis
3. Liquefactive necrosis
4. Gangrenous necrosis
5. Fat necrosis
6. Necrosis of epithelium
7. Sequelae to oncotic necrosis
8. Cell death by apoptosis

Question 9

What is Coagulative necrosis typically caused by?

Answer 9

Hypoxia, ischemia, or toxic injury

Question 10

Coagulative necrosis image + description

Question 11

Caseous necrosis image here + description

Question 12

Liquefactive necrosis image + description

Question 13

Gangrenous necrosis image (wet) + description

Question 14

Gangrenous necrosis image + description

Question 15

What are the three types of fat necrosis?

Answer 15

• Enzymatic:
◦ Occurs secondary to leakage of pancreatic enzymes (lipases) in cases of pancreatitis
• Traumatic:
◦ Blunt trauma or chronic pressure against bony prominences (subcutaneous adipose tissue in recumbent animals)
• Idiopathic (unknown cause): ◦ Necrosis of abdominal fat in overconditioned cattle

Question 16

Enzymatic fat necrosis

Question 17

Idiopathic fat necrosis image here

Question 18

Necrosis of epithelium can occur in?

Answer 18

Any epithelial surface

Question 19

What are the two types of necrosis epithelium?

Answer 19

• Erosion: Superficial sloughing or exfoliation of dead cells (without rupture of basement membrane)
• Ulcer: Full-thickness necrosis of the epithelium (with rupture of basement membrane)

Question 20

What does sequelae to Oncotic necrosis elicit?

Answer 20

An inflammatory reaction

Question 21

What happens as a result of sequelae oncotic necrosis?

Answer 21

• Formation of a sequestrum (foreign material and bone fragments)
• Inflammation with regeneration
• Inflammation with scar formation

Question 22

Sequelae to oncotic necrosis image

Question 23

What is physiologic apoptosis?

Answer 23

◦ Programmed cell destruction during embryogenesis
◦ Involution of organs or tissues deprived of hormonal stimulation (endometrial and uterine involution)
◦ Cell deletion in proliferating cell populations (to keep homeostasis). Epithelial cells of the skin, gut, etc..

Question 24

What causes pathological apoptosis?

Answer 24

Injury from toxins, ROS

Question 25

What happens as a result of pathological apoptosis?

Answer 25

◦ Mitochondria and DNA damage (radiation, anticancer drugs)
◦ Mediated by cytotoxic T lymphocytes and NK cells
◦ Nutrient deprivation

Question 26

What is pathological apoptosis regulated by?

Answer 26

◦ *** regulated by pro-apoptic and anti-apoptotic intracellular proteins*** **** that activate gene and enzymes leading to cell death****

Question 27

What is the purpose of pathological apoptosis?

Answer 27

***Purpose: Eliminates unwanted, potentially harmful, useless, damaged cells***

Question 28

What is pathological apoptosis morphological characterized by?

Answer 28

Condensation and shrinkage of the cell

Question 29

What does sequelae to Oncotic necrosis elicit?

Answer 29

An inflammatory reaction

Question 30

Necrosis of epithelium can occur in?

Answer 30

Any epithelial surface